Method for protecting a human being against health impairment by ingestion of a transdermal therapeutic system

ABSTRACT

A method for the protection of a human being against any health impairment as a result of the ingestion of the whole or parts of a transdermal therapeutic system containing at least one pharmacologically active ingredient, which is toxic or induces nausea or addiction at oral, but not at transdermal administration is disclosed. The method comprises adding to said transdermal therapeutic system a substance being able to keep off a human being from said ingestion.

[0001] This is a continuation-in-part application of application Ser.No. 09/486,214 filed May 3, 2000.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to a method for the protection of ahuman being against any health impairment as a result of the ingestionof the whole or parts of a transdermal therapeutic system (TTS). Morespecifically, the present invention relates to a method for theprotection of a human being against any health impairments as a resultof the ingestion of the whole or parts of a transdermal therapeuticsystem, comprising at least one pharmacologically activeingredient-containing, especially a pressure-sensitive adhesive layerand at least on active-ingredient-impermeable backing layer, and furthercomprising a substance, which does not interact with thepharmacologically active ingredient and is able to keep off a humanbeing from said ingestion.

[0004] 2. Description of the Prior Art

[0005] A series of transdermal therapeutic systems present an acutedanger of undesired side effects if administered orally by a human beingin order to extract a soluble active agent. This is true whether thesystem is a new one or a used one. For example, infants have a tendencyto stick anything interesting into their mouths and to at least suck orchew on it. This cannot be avoided especially if children happen toattain access to such systems by chance, especially systems with arelease liner.

[0006] Such incidents have not yet been known to occur, but thepharmaceutical authorities increasingly fear that they might and havetherefore, in various instances, demanded childproof packages. Suchchildproof packages have, in fact, been developed in variousembodiments. However, they do not protect a child from putting a TTS inhis or her mouth once the package has been opened or if the childsomehow gets hold of a used patch. Especially in the case of a TTS withactive substances such as anesthetics, analgesics, tranquilizers, orpsychopharmacological agents, an oral abuse can lead to serious healthimpairments. On the other hand, addicts could be tempted to extract suchactive agents from transdermal therapeutic systems by means of suckingor chewing.

[0007] It is known that drinkable ethyl alcohol can be denatured andthen put on the market as a methylated spirit in order to keep offpeople to drink it. A corresponding treatment of pharmaceutical dosageforms, particularly transdermal therapeutic systems, on the other hand,has not yet been published.

SUMMARY OF THE INVENTION

[0008] It is an object of the present invention to develop a method forthe protection of a human being in a way that makes an oral abuse of thekind mentioned above impossible.

[0009] It is another object of the present invention to avoid adisadvantageous change in the transdermal therapeutic system'spharmacologically active ingredient.

[0010] To achieve these objects, the method according to the presentinvention proposes the addition of a pharmacologically neutral,non-interacting substance with a disgusting taste, with an irritatingeffect on the tongue and/or the oral mucosa of a human being, or withthe property to induce nausea. Because this substance causes extremelyunpleasant and unexpected experiences with respect to taste or causesnausea, a first oral contact with the TTS according to the presentinvention is sufficient for achieving a spontaneous reaction with theeffect of immediately spitting out the corresponding patch. Thus, thepresent invention prevents children or drug addicts from an improper,i.e. oral, application of the active substance contained in the patch.

[0011] These and other objects of the invention may occur to thoseskilled in the art from the description to follow and from the appendedclaims.

DETAILED DESCRIPTION OF THE INVENTION

[0012] One embodiment of the present invention provides that a substanceis used for the addition to of a transdermal therapeutic system whichcauses nausea and thus spoils the temptation of oral application for theperson concerned.

[0013] Another embodiment of the method according to the presentinvention provides that the substance is applied on top of the activesubstance-containing layer in a separate, extremely thin layer whichdoes not prevent the permeation of the active substance. This has thebenefit that the experiencing of an extremely disgusting taste directlyupon first contact of the TTS with the oral mucosa or the tongue willdissuade further oral contact.

[0014] As a further measure, the substance can additionally be appliedto the backing layer in a separate, preferably very thin layer, thussafely achieving a further intensification of the effect ofdenaturation.

[0015] In this case, the separate substance layer is to be applied in athickness of between 10 and 100 μm, preferably between 5 and 20 μm.

[0016] An especially advantageous embodiment of the invention furtherprovides for the use of a substance which causes an irritation such as aburning of the oral mucosa and the tongue. One such negative experienceshould suffice to lastingly dissuade a child or an addict from furtherattempts at oral contact with a TTS. A similar effect can also beachieved if a substance is used which causes an intensely bitter tasteand especially an aftertaste.

[0017] An effective embodiment of the method according to the presentinvention provides for the use of substances selected form the groupconsisting of gallic acid, quinine, tannin, angostura, caffeine,lobeline, tea tree oil, certain hyphomycete cultures, denatured orcoagulated substances, turpentine or ammonia as amaroids having adisgusting taste and/or irritating effect on the tongue and/or mucosa ofa human being, and the use of emetine being able to induce nausea.

[0018] The above substances can be added to one or more layers of a TTSin a relative wide range of amount, depending on the kind of theproperties of the substances.

[0019] An embodiment of the method according to the present inventionprovides that a substance having a disgusting taste and/or an irritatingeffect on the tongue or mucosa are applied in an amount of from 0.1 to1.5 g, preferably in an amount of from 0.2 to 0.8 g to a single TTS.

[0020] Another embodiment of the method according to the presentinvention provides, that substances causing nausea, particularlyemetine, are applied in an mount from 0.01 to 0.1 g, preferably in anamount of from 0.02 to 0.05 g to a single TTS.

[0021] For the implementation of one embodiment of the method, theinvention provides for the incorporation of the substances in a filmlayer with which pharmacologically active-ingredient containing layerand, depending on the case, also the backing layer are coated. Anespecially advantageous solution provides for the use of a film layersoluble in saliva.

[0022] The method is uncomplicated and effective and protects childrenand/or addicts against health impairment by ingestion of the whole orparts of a transdermal therapeutic system. Thus, the method and the TTSaccording to the present invention present an ideal means of achievingthe objects as mentioned above.

[0023] The invention has been described in detail, with particularemphasis having been placed on the preferred embodiments, but variationsand modifications within the spirit and scope of the invention may occurto those skilled in the art to which it pertains.

I claim:
 1. A method for the protection of a human being against anyhealth impairment by ingestion of the whole or parts of a transdermaltherapeutic system, containing at least one pharmacologically activeingredient, which is toxic and/or induces nausea or addiction at oral,but not trandermal administration, which comprises adding to saidtransdermal therapeutic system an effective amount of a substance, whichdoes not interact to said pharmacologically active ingredient and isable to keep off a human being from said ingestion of the whole or partsof said transdermal therapeutic system.
 2. The method according to claim1, wherein the transdermal therapeutic system comprises at least onelayer containing said pharmacologically active ingredient, apressure-sensitive adhesive layer and at least one backing layer beingimpermeable to the pharmacologically active ingredient.
 3. The methodaccording to claim 2, wherein the pharmacologically active ingredientcontaining layer and the pressure-sensitive adhesive layer areidentical.
 4. The method according to claim 2, wherein the transdermaltherapeutic system contains said added substance in at least one layerselected from the group consisting of pharmacologically activeingredient containing layer, pressure-sensitive adhesive layer andbacking layer.
 5. The method according to claim 2, comprising applyingsaid substance as a film layer on the layer containing thepharmacologically active ingredient.
 6. The method according to claim 5,comprising applying said substance layer in a thickness of between 10and 100 μm.
 7. The method according to claim 2 comprising applying saidsubstance film layer on the active ingredient impermeable backing layer.8. The method according to claim 7 comprising applying said substancelayer in a thickness of between 10 and 100 μm.
 9. The method accordingto claim 1, wherein the added substance has an adverse disgusting orbitter taste and/or irritates the tongue and/or the oral mucosa of ahuman being.
 10. The method according to claim 1, wherein the addedsubstance induces nausea.
 11. The method according to claim 9 comprisingadding the substance in an amount of from 0.1 to 1.5 g.
 12. The methodaccording to claim 9 comprising adding the substance in an amount offrom 0.2 to 0.8 g.
 13. The method according to claim 10 comprisingadding the substance in an amount of from 0.01 to 0.1 g.
 14. The methodaccording to claim 10 comprising adding the substance in an amount offrom 0.02 to 0.05 g.
 15. The method according to claim 1, wherein theadded substance is selected from the group consisting of gallic acid,quinine, tannin, caffeine, lobeline, tea tree oil, hyphomycete cultures,turpentine, angostura and emetine.
 16. The method according to claim 1,wherein said pharmacologically active ingredient is selected from thegroup consisting of anesthetics, analgesics, tranquilizers andpsychoactive drugs.